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Q08351 · TPOR_MOUSE

  • Protein
    Thrombopoietin receptor
  • Gene
    Mpl
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Receptor for thrombopoietin that regulates hematopoietic stem cell renewal, megakaryocyte differentiation, and platelet formation (PubMed:8630375, PubMed:9122198, PubMed:9639492).
Upon activation by THPO, induces rapid tyrosine phosphorylation and activation of JAK2, providing docking sites for many signaling proteins such as STAT5, SHIP/INPP5D, GRB2, SOS1 and PI3K. In turn, These signaling cascades lead to the proliferation, survival, and differentiation of megakaryocytes, ultimately leading to increased platelet production

Isoform Mpl-tr

Acts as an inhibitor of thrombopoietin signaling by promoting protein down-regulation of full-length isoform Mpl-fl.

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentcell surface
Cellular ComponentGolgi apparatus
Cellular Componentplasma membrane
Molecular Functionthrombopoietin receptor activity
Biological Processdefinitive hemopoiesis
Biological Processhomeostasis of number of cells
Biological Processnegative regulation of apoptotic process
Biological Processplatelet formation
Biological Processpositive regulation of gene expression
Biological Processregulation of chemokine production
Biological Processregulation of stem cell division
Biological Processregulation of stem cell proliferation
Biological Processthrombopoietin-mediated signaling pathway

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Thrombopoietin receptor
  • Short names
    TPO-R
  • Alternative names
    • Myeloproliferative leukemia protein
    • Proto-oncogene c-Mpl
  • CD Antigen Name
    • CD110

Gene names

    • Name
      Mpl
    • Synonyms
      Tpor

Organism names

  • Taxonomic identifier
  • Strains
    • ICFW
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q08351
  • Secondary accessions
    • A6H8H6
    • Q8BRX0

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Single-pass type I membrane protein
Golgi apparatus
Cell surface

Features

Showing features for topological domain, transmembrane.

Type
IDPosition(s)Description
Topological domain26-482Extracellular
Transmembrane483-504Helical
Topological domain505-625Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Mpl-deletion mice produce residual numbers of platelets that are sufficient to prevent bleeding and allow normal survival.

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis104Completely abrogated binding to THPO.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 46 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for signal, chain, glycosylation, cross-link, modified residue.

Type
IDPosition(s)Description
Signal1-25
ChainPRO_000001098826-625Thrombopoietin receptor
Glycosylation117N-linked (GlcNAc...) asparagine
Cross-link544Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link564Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue616Phosphotyrosine
Modified residue621Phosphotyrosine

Post-translational modification

Ubiquitination at Lys-544 and Lys-564 targets MPL for degradation by both the lysosomal and proteasomal pathways. The E3 ubiquitin-protein ligase CBL significantly contributes to this ubiquitination.

Keywords

Proteomic databases

PTM databases

Expression

Induction

Expression in the bone marrow displays diurnal rhythmicity (a circadian rhythm that is synchronized with the day/night cycle).

Gene expression databases

Interaction

Subunit

Homodimer (PubMed:38326297).
Interacts with ATXN2L. Interacts with JAK2 and TYK2; these interactions increase MPL localization to the cell membrane. Interacts with THPO (PubMed:38326297).
Interacts with SHIP/INPP5D. Interacts with kinases BTK and SYK (By similarity).

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for domain, motif.

Type
IDPosition(s)Description
Domain178-270Fibronectin type-III 1
Domain383-479Fibronectin type-III 2
Motif465-469WSXWS motif
Motif519-527Box 1 motif

Domain

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 2 isoforms produced by Alternative splicing.

Q08351-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    Mpl-fl
  • Synonyms
    Mpl-full-length
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    625
  • Mass (Da)
    69,788
  • Last updated
    2011-07-27 v2
  • MD5 Checksum
    E6F0F2183BE99FA18589D041DD674FDF
MPSWALFMVTSCLLLALPNQAQVTSQDVFLLALGTEPLNCFSQTFEDLTCFWDEEEAAPSGTYQLLYAYRGEKPRACPLYSQSVPTFGTRYVCQFPAQDEVRLFFPLHLWVKNVSLNQTLIQRVLFVDSVGLPAPPRVIKARGGSQPGELQIHWEAPAPEISDFLRHELRYGPTDSSNATAPSVIQLLSTETCCPTLWMPNPVPVLDQPPCVHPTASQPHGPAPFLTVKGGSCLVSGLQAGKSYWLQLRSQPDGVSLRGSWGPWSFPVTVDLPGDAVTIGLQCFTLDLKMVTCQWQQQDRTSSQGFFRHSRTRCCPTDRDPTWEKCEEEEPRPGSQPALVSRCHFKSRNDSVIHILVEVTTAQGAVHSYLGSPFWIHQAVLLPTPSLHWREVSSGRLELEWQHQSSWAAQETCYQLRYTGEGREDWKVLEPSLGARGGTLELRPRARYSLQLRARLNGPTYQGPWSAWSPPARVSTGSETAWITLVTALLLVLSLSALLGLLLLKWQFPAHYRRLRHALWPSLPDLHRVLGQYLRDTAALSPSKATVTDSCEEVEPSLLEILPKSSESTPLPLCPSQPQMDYRGLQPCLRTMPLSVCPPMAETGSCCTTHIANHSYLPLSYWQQP

Q08351-2

  • Name
    Mpl-tr
  • Synonyms
    Mpl-truncated
  • Note
    Rbm15 regulates the production of isoform Mpl-tr.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 428-457: VLEPSLGARGGTLELRPRARYSLQLRARLN → ETEACFVALASRPTPGPRPVPQRHCSPKSF
    • 458-625: Missing

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
E9Q7U5E9Q7U5_MOUSEMpl465
A2A9D4A2A9D4_MOUSEMpl633
Q925F5Q925F5_MOUSEMpl566

Features

Showing features for sequence conflict, alternative sequence.

Type
IDPosition(s)Description
Sequence conflict1-7in Ref. 2; CAA52031
Sequence conflict99in Ref. 2; CAA52031
Sequence conflict222in Ref. 2; CAA52031
Sequence conflict241in Ref. 1; CAA80365, 2; CAA52031 and 5; AAI46614
Alternative sequenceVSP_059621428-457in isoform Mpl-tr
Alternative sequenceVSP_059622458-625in isoform Mpl-tr

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
Z22649
EMBL· GenBank· DDBJ
CAA80365.1
EMBL· GenBank· DDBJ
mRNA
Z22657
EMBL· GenBank· DDBJ
CAA80372.1
EMBL· GenBank· DDBJ
Genomic DNA
X73677
EMBL· GenBank· DDBJ
CAA52031.1
EMBL· GenBank· DDBJ
mRNA
AK041166
EMBL· GenBank· DDBJ
BAC30846.1
EMBL· GenBank· DDBJ
mRNA
AL627212
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC146613
EMBL· GenBank· DDBJ
AAI46614.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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